人参皂苷Re对阿尔茨海默病模型小鼠脑组织生物标记物调控作用的研究

Protective effect of ginsenoside Re on biomarkers in mice with Alzheimer's disease

目的通过超高速液相色谱-质谱联用(UPLC-MS)技术研究人参皂苷Re(G-Re)对阿尔茨海默病(AD)模型小鼠生物标记物的调控作用以及机制,为AD的中药治疗提供新思路。方法将小鼠随机分为对照组、AD模型组和G-Re治疗组,通过免疫组化实验观察小鼠脑部海马区细胞的病理学改变,运用以UPLC-MS为基础的代谢组学技术研究G-Re对AD模型小鼠脑组织生物标记物的调控作用。结果免疫组化实验发现,对照组小鼠海马区无Aβ沉积,AD模型组小鼠海马区可见大量Aβ沉积,经G-Re治疗后小鼠海马区Aβ沉积明显减少。代谢组学分析发现,AD模型组小鼠脑组织中存在次黄嘌呤、次黄嘌呤核苷、苯丙氨酸、16碳鞘氨醇、植物鞘氨醇、溶血磷脂酰胆碱C16:0、溶血磷脂酰胆碱C18:1、溶血磷脂酰胆碱C18:0等9种生物标记物。与对照组比较,AD组次黄嘌呤、次黄嘌呤核苷和苯丙氨酸的含量明显升高(P<0.05),16碳鞘氨醇、植物鞘氨醇、溶血磷脂酰胆碱(C16:0、C18:1、C18:0)的含量明显降低(P<0.05)。经G-Re干预后,AD组小鼠脑组织中次黄嘌呤、次黄嘌呤核苷和苯丙氨酸的含量明显降低(P<0.05),16碳鞘氨醇、植物鞘氨醇、溶血磷脂酰胆碱(C16:0、C18:1、C18:0)的含量明显升高(P<0.05)。结论 G-Re可以干预AD小鼠体内氨基酸、核酸及脂质等代谢途径,减少小鼠海马区的Aβ沉积,从而对AD起到治疗作用。

Objective To investigate the effect of ginsenoside Re（ G-Re） on biomarkers in an Alzheimer＇s disease（ AD） mouse model based on UPLC-MS,and to provide new ideas for traditional Chinese medicine treatment of AD. Methods Twenty-four mice were randomly divided into control group,AD model group and G-Re treatment group with eight mice in each group. Pathological changes in the hippocampus were assessed by immunohistochemistry. UPLC/MS-based metabolomics was used to identify biomarkers which were differentially expressed in the brains of AD mice. Results The hippocampal amyloid deposition increased in AD mice,and it was ameliorated by the treatment of G-Re.A total of 9 potential biomarkers were identified,which were associated with the metabolism of purine,amino acids,sphingolipids and lysophosphatidylcholines in AD mice. Compared to control group,the peak intensities of 9 biomarkers give a pronounced change in AD（ P〈0. 05）. G-Re treatment affected all these metabolic pathways. Conclusions These results indicate that G-Re can reduce the hippocampal amyloid deposition in AD mice by regulation of related brain metabolic pathways. In a word,G-Re plays a positive role in the treatment of AD.